Aalaa Mahmoud Ahmed Shawqi Mahmoud, Emad Shash, Hayam Ateyya, Farida A Okasha, Nouran Omar El Said
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引用次数: 0
Abstract
Background: Paclitaxel-induced peripheral neuropathy (PIPN) is a condition that persists chronically in more than 60% of affected individuals, and currently there are no proven PIPN prophylaxis. Pre-clinical data suggest the angiotensin-II-receptor blocker losartan may attenuate neuro-inflammation and nerve injury. This study was conducted to assess losartan's neuroprotective effect against PIPN in patients with breast cancer.
Methods: In this single-center, open-label, randomized, controlled trial, women with early-stage breast cancer scheduled for weekly paclitaxel (80 mg/mg2 or 12 doses) were enrolled and randomized 1:1 to losartan 100 mg once daily plus standard care or standard care alone. The primary end point was incidence of grade 2 or higher neuropathy, per National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE v5.0). Secondary end points included time-to-neuropathy (in days), patient quality of life (QoL) assessed by Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX), pain intensity using visual-analogue scale (VAS), serum nerve growth factor (NGF) levels, and safety.
Results: Between December 2023 and December 2024, 89 Patients Were Randomized (Losartan, n = 45; Control, n = 44). Losartan Significantly Reduced Grade ≥ 2 Neuropathy Incidence (33.3% vs. 86.4%, p < 0.001) and Delayed Its Onset (73.27 vs. 43.75 Days; Hazards Ratio [HR] = 0.2, 95% Confidence Interval [CI]: 0.11-0.35) Compared With Standard Care Alone, Respectively. At 12 Weeks, Patients Treated With Losartan Reported Superior QoL (FACT/GOG-NTX: 31.87 ± 6.43 vs. 15.45 ± 10.04; p < 0.001) and Reduced Pain Scores (Median VAS 3 vs. 8; p < 0.001) Compared With Standard Care Alone, Respectively. NGF Levels Were Comparable and Adverse Events Were Similar Between Groups.
Conclusions: Daily losartan reduced and delayed clinically significant paclitaxel-induced neuropathy while improving patient-reported outcomes, without additional toxicity. These findings support repurposing losartan as a low-cost PIPN prophylactic and justify validation in larger, multicenter trials.
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Pharmacotherapy is devoted to publication of original research articles on all aspects of human pharmacology and review articles on drugs and drug therapy. The Editors and Editorial Board invite original research reports on pharmacokinetic, bioavailability, and drug interaction studies, clinical trials, investigations of specific pharmacological properties of drugs, and related topics.
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